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dc.contributor.authorPeart, Jason N
dc.contributor.authorHoe, Louise See
dc.contributor.authorPepe, Salvatore
dc.contributor.authorJohnson, Peter
dc.contributor.authorHeadrick, John P
dc.date.accessioned2017-05-03T11:16:49Z
dc.date.available2017-05-03T11:16:49Z
dc.date.issued2012
dc.identifier.issn1549-1684
dc.identifier.doi10.1089/rej.2011.1226
dc.identifier.urihttp://hdl.handle.net/10072/47767
dc.description.abstractWe test the hypothesis that moderate calorie restriction (CR) reverses negative influences of age on molecular determinants of myocardial stress resistance. Postischemic contractile dysfunction, cellular damage, and expression of regulators of autophagy/apoptosis and of prosurvival and prodeath kinases were assessed in myocardium from young adult (YA; 2- to 4-month-old) and middle-aged (MA; 12-month-old) mice, and MA mice subjected to 14 weeks of 40% CR (MA-CR). Ventricular dysfunction after 25%Ქ), as was cell death indicated by troponin I (TnI) efflux (1,701Ჱ4?ng vs. 785ᱰ2?ng in YA). MA hearts exhibited 30% and 65% reductions in postischemic Beclin1 and Parkin, respectively, yet 50% lower proapoptotic Bax and 85% higher antiapoptotic Bcl2, increasing the Bcl2/Bax ratio. Age did not influence Akt or p38-mitogen-activated protein kinase (MAPK) expression; reduced expression of increasingly phosphorylated ribosomal protein S6 kinase (p70S6K), increased expression of dephosphorylated glycogen synthase kinase 3ߠ(GSK3ߩ and enhanced postischemic p38-MAPK phosphorylation. CR countered the age-related decline in ischemic tolerance, improving contractile recovery (60%ᴥ) and reducing cell death (123Ჲ?ng of TnI). Protection was not associated with changes in Parkin or Bax, whereas CR partially limited the age-related decline in Beclin1 and further increased Bcl2. CR counteracted age-related changes in p70S6K, increased Akt levels, and reduced p38-MAPK (albeit increasing preischemic phosphorylation), and paradoxically reduced postischemic GSK3ߠphosphorylation. In summary, moderate age worsens cardiac ischemic tolerance; this is associated with reduced expression of autophagy regulators, dysregulation of p70S6K and GSK3߬ and postischemic p38-MAPK activation. CR counters age effects on postischemic dysfunction/cell death; this is associated with reversal of age effects on p70S6K, augmentation of Akt and Bcl2 levels, and preischemic p38-MAPK activation. Age and CR thus impact on distinct determinants of ischemic tolerance, although p70S6K signaling presents a point of convergence.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherMary Ann Liebert
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom59
dc.relation.ispartofpageto70
dc.relation.ispartofissue1
dc.relation.ispartofjournalRejuvenation Research
dc.relation.ispartofvolume15
dc.rights.retentionY
dc.subject.fieldofresearchCardiology (incl. cardiovascular diseases)
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchMedical physiology
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchcode320101
dc.subject.fieldofresearchcode3202
dc.subject.fieldofresearchcode3208
dc.subject.fieldofresearchcode3101
dc.titleOpposing Effects of Age and Calorie Restriction on Molecular Determinants of Myocardial Ischemic Tolerance
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Health, School of Medical Science
gro.date.issued2015-06-12T05:04:06Z
gro.hasfulltextNo Full Text
gro.griffith.authorHeadrick, John P.
gro.griffith.authorPeart, Jason N.


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